Ganong's Review of Medical Physiology, 23rd Edition

344 SECTION IV Endocrine & Reproductive Physiology
FIGURE 22–8 Hormone synthesis in the zona glomerulosa.
The zona glomerulosa lacks 17α-hydroxylase activity, and only the
zona glomerulosa can convert corticosterone to aldosterone because
it is the only zone that normally contains aldosterone synthase. ANG II,
angiotensin II.
TABLE 22–1 Principal adrenocortical
hormones in adult humans. a
Name Synonyms
Cortisol Compound F,
hydrocortisone
Average Plasma
Concentration
(Free and
Bound) a
(μg/dL)
13.9 10
Corticosterone Compound B 0.4 3
Average
Amount
Secreted
(mg/24 h)
Aldosterone 0.0006 0.15
Deoxycorticosterone
Dehydroepiandrosterone
sulfate
Cholesterol
ACTH
ANG II
Pregnenolone
Progesterone
Deoxycorticosterone
Aldosterone
synthase
Corticosterone
HO
Aldosterone
synthase
ANG II
O
18-Hydroxycorticosterone
Aldosterone
synthase
O
Aldosterone
HO
CH2OH C
CH2 O
O
CH2OH HC
C O
DOC 0.0006 0.20
DHEAS 175.0 20
aAll plasma concentration values except DHEAS are fasting morning values after
overnight recumbency.
HO
Cortisol
and
sex steroids
CLINICAL BOX 22–1
Synthetic Steroids
As with many other naturally occurring substances, the activity
of adrenocortical steroids can be increased by altering
their structure. A number of synthetic steroids are available
that have many times the activity of cortisol. The
relative glucocorticoid and mineralocorticoid potencies of
the natural steroids are compared with those of the synthetic
steroids 9α-fluorocortisol, prednisolone, and dexamethasone
in Table 22–2. The potency of dexamethasone
is due to its high affinity for glucocorticoid receptors and its
long half-life. Prednisolone also has a long half-life.
STEROID BIOSYNTHESIS
The major paths by which the naturally occurring adrenocortical
hormones are synthesized in the body are summarized in Figures
22–7 and 22–8. The precursor of all steroids is cholesterol.
Some of the cholesterol is synthesized from acetate, but most of
it is taken up from LDL in the circulation. LDL receptors are especially
abundant in adrenocortical cells. The cholesterol is esterified
and stored in lipid droplets. Cholesterol ester hydrolase
catalyzes the formation of free cholesterol in the lipid droplets
(Figure 22–9). The cholesterol is transported to mitochondria by
a sterol carrier protein. In the mitochondria, it is converted to
pregnenolone in a reaction catalyzed by an enzyme known as
cholesterol desmolase or side-chain cleavage enzyme. This enzyme,
like most of the enzymes involved in steroid biosynthesis,
is a member of the cytochrome P450 superfamily and is also
known as P450scc or CYP11A1. For convenience, the various
TABLE 22–2 Relative potencies of
corticosteroids compared with cortisol. a
Steroid
Glucocorticoid
Activity
Mineralocorticoid
Activity
Cortisol 1.0 1.0
Corticosterone 0.3 15
Aldosterone 0.3 3000
Deoxycorticosterone 0.2 100
Costisone 0.7 0.8
Prednisolone 4 0.8
9α-Fluorocortisol 10 125
Dexamethasone 25 –0
a Values are approximations based on liver glycogen deposition or anti-inflammatory
assays for glucocorticoid activity, and effect on urinary Na + /K + or maintenance
of adrena-lectomized animals for mineralocorticoid activity. The last three steroids
listed are synthetic compounds that do not occur naturally.